Biomedical Research

ContactTechnology Transfer Interface+32 (0)2 629 22 07 | rd.interface@vub.ac.be | www.vubtechtransfer.be

Aude Bonehill, PhDUniversity Medical Center Research Manager+32 (0)2 477 55 50 | aude.bonehill@vub.ac.be | www.uzbrussel.be

3Biomedical research at the University Medical Center Brussels Today more than ever, our society is facing many challenges in the field of health. Health research at the University Medical Center Brussels merges scientific expertise of various research teams into 10 specialized clusters. Each cluster consists of several research groups performing basic, pharmaceutical, translational, clini-cal or medical-sociological research. A main objective is the development of more personalized medicine, with medical decisions, practices, and treatment being tailored to the individual patient.

Nine clusters focus on the following major health challenges: Medicalimaging Cardiovasculardisorders Centralnervoussystemdisorders Developmentandageing Diabetes Liverdisorders Oncology Reproduction,geneticsandregenerativemedicine Publichealth

In addition, one cluster combines all pharmaceutical research associated in the Pharmaceutical Institute.Fundamental, translational and clinical research is performed at the UniversityMedical Center Brussels, which includes the FacultyofMedicineandPharmacyoftheVrijeUniversiteitBrussel and the university hospital UZ Brussel located nearby. With its 700 beds, nearly 30,000 inpatients and 500,000 outpatients are treated yearly. Moreover, close to 350 clinical studies are performed every year, including both academic and industry sponsored phase I-IV trials. Clinical trials are supported centrally by a ClinicalTrialCenter, which pro-vides assistance in the design, quality control and evaluation of all forms of clinical trials. Furthermore, there is a phase I unit, study nurses service, and a unit of clinical methodology and statistics.

Multidisciplinary health research is also performed in close collaboration with several research teams of the engineering,sciencesandhumanitiesfacultiesoftheVrijeUniversiteitBrussel.

With this brochure, we invite you to discover the world of biomedical research performed at the University Medical Center Brussels. You will find an extensive overview of the research conducted in a whole array of bio-medical topics. For any further questions concerning innovation and valorization, we invite you to contact the Technology Transfer Interface of the Vrije Universiteit Brussel or the University Medical Center Research Manager.

Prof. dr. Jacques De KeyserVice-Dean Research

Dr. Aude BonehillUniversity Medical Center Research Manager

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5Index

Oncology Research Center ...................................................................................................................................................................................................................... 6

C4N, Center Neurosciences .................................................................................................................................................................................................................... 8

Liver and Cell Biology and Toxicology ........................................................................................................................................................................................ 10

Research Center for Cardiovascular Diseases ...................................................................................................................................................................... 12

Public Health ....................................................................................................................................................................................................................................................... 14

Medical Imaging and Physical Sciences .................................................................................................................................................................................... 16

Diabetes Research Center ........................................................................................................................................................................................................................ 18

Pharmaceutical Research and Data Technology ............................................................................................................................................................... 21

Reproduction, Genetics and Regenerative Medecine .................................................................................................................................................. 24

Development, Ageing and Pathology .......................................................................................................................................................................................... 27

6VrijeUniversiteitBrussel-UZBrussel

OncologyResearchCenterorc.vub.ac.be

The Oncology Research Center (ORC) is a multidisciplinary group in which basic, translational and clinical investi-gators from the Vrije Universiteit Brussel (VUB) and UZ Brussel collaborate. The ORC provides the opportunity to combine different expertises, conduct studies and share information in the field of oncology. These opportunities optimize and facilitate basic, preclinical, translational, psychosocial, clinical and public health research being per-formed by scientists at the ORC.

PersonalizedCancerTreatment,Hematology,MultipleMyeloma,ImproveEnd-of-lifeCare,ResearchPalliativeCare,Immunotherapy,Radiotherapy

End-of-LifeCare(ZRL) Luc Deliens - luc.deliens@vub.ac.be

HematologyandImmunology(HEIM)Karin Vanderkerken - karin.vanderkerken@vub.ac.be

LaboratoryofMedicalandMolecularOncology(LMMO)Jacques De Grve - jacques.degreve@uzbrussel.be

LaboratoryofMolecularandCellularTherapy(LMCT)Kris Thielemans - kris.thielemans@vub.ac.be

TranslationalRadiationOncology,supportivecareandPhysics(TROP)Dirk Verellen - dirk.verellen@uzbrussel.be Mark De Ridder - mark.deridder@uzbrussel.be

Main study areas

Multiplemyeloma Cellular and molecular biology of multi-

ple myeloma In vitro molecular and cellular multiple

myeloma studies The development of a worldwide val-

idated mouse model for the study of myeloma pathogenesis and preclinical drug development

Role of immunomodulatory drugs in enhancing the efficacy of an anti-mye-loma vaccination strategy

Phase II-IV clinical trials in myeloma patients

Melanoma Messenger RNA based immunotherapy

of melanoma Inhibitory mechanisms exerted by mela-

noma cells and their environment Relationship between persistent STAT3

activation and myeloid derived suppres-sor cell-mediated immune suppression in melanoma

Phase II-III clinical trials involving den-dritic cell therapy in melanoma

CancerImmunology Multitargeted therapy: development of

novel therapeutic combinations for aug-menting the potency of cancer vaccines

Enhancing tumor immunity by intran-odal injection of mRNA encoding tumor antigens and activation stimuli

Translational research involving dendrit-ic cell therapy and clinical trials for early as well as advanced disease

Manipulation of the immune system using targeted lentiviral vectors

Cancergeneticsandtargetedtreatment Preclinical assessment of anticancer

agents with a focus on the HER pathway in BA/F3 cells

Preclinical siRNA development to specif-ically inhibit mutant receptors that are resistant to tyrosine kinase inhibitors and investigation of its in vivo application

Genetic cancer with an emphasis on breast/ovarian cancer in relationship to the Familial Cancer Clinic of the Oncology Center

Genomic biomarker research. Investiga-tor initiated translational studies in fol-lowing tumor types: lung cancer, brain tumors, melanoma, sarcoma and esoph-ageal cancer.

Palliativecareresearch FLanders study to Improve End-of-life

Care and Evaluation tools (FLIECE): study promotes better palliative care and end-of-life care by developing tools to guide clinicians and health care institutions

European Intersectorial and Multi-disciplinary Palliative Care Research Training (EUROIMPACT): study develops an educational and research training framework in end-of-life care research in Europe

International study of Place of Death (iPOD): examines cross-national patterns in place of death using death certificate data

European Sentinel Network of General Practitioners Study to Monitor End-of-Life Care (EURO SENTIMELC)

Dying well with dementia aims to pro-mote better palliative care and end-of-life care for patients with dementia in long-term-care settings and to compare the results with other countries

End-of-life decisions: implications for public health policy

The practice of terminal sedation: a multiple perspectives study

Legalization of euthanasia: the slip-pery slope hypothesis tested in Fanders, Belgium

Public views on end-of-life care

Otherresearchtopics Molecular and phenotypic characteriza-

tion of leukemic cells NK cell activity in leukemia, characteri-

zation of hematopoietic and mesenchy-mal stem cells

Pathogenesis of thrombophilia Sponsored and academic studies to

assess the tolerability and efficacy of novel systemic treatments of cancer (phase I, II, III); sponsored and academic studies

Radiobiology of colorectal cancer

Equipment& infrastructure

Cellbanks Hematopoietic stem cell bank Tumor biobank Dendritic cell bank

Cell analysis FACS AriaIII (High multicolor performance and sorting applications) FACS LSR Fortessa (High multicolor performance) FACS Canto (High multicolor performance)

Genetic analysis Sequencing GS Junior System Micro-arrays Next Generation Sequencing Platform

Biosafety(C2-C4) Retroviruslab HIV lab

Newradiationtechniques Vero stereotactic body radiotherapy

(SBRT) system. (joint product of Brainlab and MHI)

Tomotherapy Hi Art system Elekta Sli 15 accelerator Nucletron HDR Ir 192 Therapies: - Image-guided Radiotherapy - Frameless radiosurgery

Industrialcollaborationfields

Preclinical models for cancer (5TMM murine model for multiple myeloma; BA/F3 cell model; Cancer cell lines; Transfected cell lines for the study of the functionality of cancer genes, )

Phase I-III studies in the field of cancer Industrial collaborations: Galapagos,

Celgene, ISIS Pharmaceuticals, Roche, Pfizer, Centocor, Mundipharma, Merck, Boerhinger-Ingelheim, Novo Nordisk, BrainLAB, VERO gmbh, VISHAY, Novartis, Astra Zeneca, Orfit industries.

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8VrijeUniversiteitBrussel-UZBrussel

C4N,CenterforNeuroscienceswww.c4n.be

The Center for Neurosciences coordinates neuroscience-related research activities, and especially aims a lasting col-laborative research program among basic and clinical neuroscientists, allowing research from bench to bed.

Neuroprotection,Neuromodulation,Astrocyte-neuroninteractions,Stroke,Epilepsy,MultipleSclerosis,Mental functions &fatigue

ExperimentalPharmacology(EFAR)Yvette Michotte - ymichot@vub.ac.beIlse Smolders - ilse.smolders@vub.ac.be

Neurology(NEUR)Jacques De Keyser - jacques.dekeyser@uzbrussel.beRon Kooijman - ron.kooijman@vub.ac.be

PharmaceuticalBiotechnologyandMolecularBiology(MICH)Bart Rombaut - brombaut@vub.ac.beAnn Massie - amassie@vub.ac.be

CerebralResuscitationResearchGroup(CRRG)Luc Huyghens - luc.huyghens@uzbrussel.beChristian Verborgh - christian.verborgh@uzbrussel.be

9Main study areas

Development of innovative new anti-epileptic drugs, that are more effective, produce less side effects, and improve cognition. Development of drugs that prevent epileptogenesis. Main targets: astrocytes, monoamines, neuropeptides, glutamate transporters.

Acute management of stroke, with focus on revascularisation, neuroprotective interventions (IGF-1, monoamines), the role of the sympathetic nervous system, and telemedicine.

Multiple sclerosis and other neurode-generative disorders such as Parkinsons disease: pathophysiology (main target: the role of astrocytes, monoamines, glutamate transporters, IGF-1), factors that affect disease progression, and new therapeutic interventions.

Neuromodulation of affective disorders, autonomic nervous system (effects on the immune system and systemic disor-ders), and blood pressure.

The pathophysiology and management of fatigue and cognition in neurological disorders.

Development of high-throughput ana-lytical methods for monoamines, amino acids, neuropeptides and drugs.

Equipment& infrastructure

Methods &equipment: Broad range of rodent models:

- Chemical and electrical models for epileptic seizures and chronic epilepsy

- Models for Parkinsons disease: 6-hydroxydopamine and lactacystin model

- Endothelin-1 model for focal tran-sient cerebral ischemia

- Several genetic models e.g. astrocyte-specific beta2 adrenergic receptor knockout mouse

Rodent behavioural unit:- Locomotor activity: open field, rota-

tional behaviour (Rotometer), neuro-logical deficit score, Rotarod

- Spatial memory: Morris water maze for rats and mice; Y maze for mice

- Anti-depressant-like activity: forced

swim test, tail suspension test Stereotaxic surgery (rat and mouse) and

in vivo microdialysis Telemetry-based 24h video-EEG moni-

toring units for rodents Radiotelemetric cardiac monitoring

units Broad range of analytical equipment:

- Liquid chromatography with electro-chemical, fluorescence or ultraviolet detection for the quantification of neurotransmitters and drugs

- Nano liquid chromatography coupled to tandem mass spectrometry for the determination of neuropeptides and drugs

- Capillary electrophoresis- Size exclusion chromatography

Protein and DNA/RNA electrophoresis Doppler flowmetry Cell cultures (growth of neuroviruses,

cell infections, quantification) and transfection

Immunobiotechnological techniques: (immuno)histochemistry, Western blot-ting, ELISA

Brain histology, fluorescence microscopy Nanobodies Molecular biology techniques, DNA

microarrays, real-time PCR

Clinicalfacilities: Clinical neurophysiology (EEG, MEP, vis-

ual, auditory and somatosensory evoked potentials, event-related potentials, EMG, EEG-video monitoring)

Doppler (transcranial, cervical) Stroke unit with monitoring MR scanning of the brain (MR spectros-

copy, perfusion) PET and SPECT scan of the brain Magstim super rapid stimulator for

repetitive transcranial magnetic stimu-lation and neuronavigaton system

Electroconvulsive therapy Nervus vagus stimulation Transcranial direct stimulation system Multiple exercise equipment (ergom-

eters, treadmill, rotarod) Eye-tracking equipment Climatic chamber for exercise & clini-

cal testings (high & low temperature, humidity)

EEG 64 channel equipment

Nexus 10 psychophysiological monitoring Life shirt (HRV, core temperature,) Core and skin temperature measurement Reaction time test Attention and learning tests Neurocognitive test batteries Dual belt treadmill (spinal cord, MS,

stroke patients testing)

Industrialcollaborationfields

Preclinical models for neuroprotection and neuromodulation, especially in the field of epilepsy, stroke, Parkinsons dis-ease and multiple sclerosis

Phase I III studies in the field of stroke and multiple sclerosis

Telemedicine Consultancy support in the field of

stroke, epilepsy and multiple sclerosis Preclinical and clinical studies on vagus

nerve stimulation Repetitive transcranial magnetic stimu-

lation Neurophysiological studies in the field

of exercise, fatigue and cognition

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VrijeUniversiteitBrussel-UZBrussel

LiverandCellBiology&ToxicologyYearly, 60,000 European citizens die due to liver failure, and at least ten times more are chronically affected and disa-bled by liver disorders. There is currently no curative treatment, and liver transplantation often becomes the ultimate solution, which is only available to a small fraction of patients due to shortage of donors. The cluster Liver and Cell Biology and Toxicology endeavors to find new and better treatment options by investigating mechanisms regulating the function of liver cells in health and disease. Specifically, finding of new drug targets for the treatment of acute and chronic liver conditions is one of the clusters main goals. At the same time, liver cell therapy options based on hepatic progenitors and postnatal stem cells are explored. Stem cell-derived liver cells, as well as primary hepatic cells, could also be used to construct in vitro liver models for toxicity testing of new drug candidates and chemicals in general. Such systems could potentially replace or at least reduce the use of experimental animals in safety studies, but more importantly, contribute to more accurate prediction of hepatotoxic potential of new drug candidates and alike. The lat-ter remains an important socio-economical problem being the most frequent safety related reason of post-marketing drug withdrawal and an important cause of acute liver failure. Consequently, development of metabolically-competent in vitro liver models applicable in the industrial settings is one of the most prominent research domains within the Liver and Cell Biology & Toxicology cluster.

Invitrotoxicology,alternative3Rmethods,stemcells,primaryhepatocytes,cosmeticsafety,chronicliverdisease,hepaticstellatecell,liverprogenitorcell,liverregeneration,autoinflammation,autoallergy,immunomodulation,stemcells,immunotherapy

InVitroToxicologyandDermato-Cosmetology(IVTD) Vera Rogiers - vera.rogiers@vub.ac.be ivtd-fafy.be

LiverCellBiologyLab(LIVR)Leo van Grunsven lvgrunsv@vub.ac.becyto.vub.ac.be

ImmunologyoftheSkin(I-SKIN)Jan Gutermuth jan.gutermuth@vub.ac.be

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Main study areas

InVitroToxicologyandDermato-Cosmetology(IVTD) In vitro toxicology:

Development of metabolically-com-petent in vitro liver models based on: - Primary hepatocytes by (i) explor-

ing epigenetic mechanisms of gene regulation i.e. histone acetylation, DNA methylation, microRNAs (ii) and (iii) immortalization of primary hepatocytes

- Stem cells isolated from various human postnatal tissues, i.e. skin, adipose tissue and Whartons jelly, by (i) careful characterization, (ii) in vitro expansion and (iii) differentia-tion towards the hepatic phenotyp,

- A coating substratum and 3D cell cultivation scaffold derived from decelullarized liver matrix

Safety assessment of dermato-cosmetic substances based on non-invasive bioengineering and in vitro methodology

Clinical research:Targeting intercellular communication in the treatment of acute and chronic liver diseases and potential use of stem cells in end-stage liver disorders

LiverCellbiologyLab(LIVR) Investigation of mechanisms involved in

hepatic stellate cell activation in vitro and in vivo; studies on autophagy, ER stress, histone modifications and miRNA involvement

The hepatic progenitor cell niche under experimental conditions and in human liver disease

I-SKINLab Functional characterization of stem

cells for immunomodulatory capacities (Dendritic cell-T cell-stem cell coculture system)

Development of preclinical models of asthma, eczema and autoimmunity

Evaluation of the therapeutic potential of stem cells in preclinical models

Evaluation of the adipose tissue derived stem cells in chronic ulcers

Equipmentandinfrastructure

InVitroToxicologyandDermato-Cosmetology(IVTD) Biosafety level 2 laboratory and culture

facilities Organ perfusion unit Scintillation counter (TriCarb 2810 TR;

Perkin Elmer) Fluorescence microscope (Nikon Eclipse Ti) 2 RTqPCR termal cyclers (Step One Plus;

Applied Biosystems, iQ5; Bio-Rad) Microplate reader (Victor3; Perkin-

Elmer) Micro-volume UV spectrophotometer (NanoDrop 2000c; Thermo SCIENTIFIC)

LiverCellbiologyLab(LIVR) Protein and DNA/RNA electrophoresis Cell sorter, FACSAria (Becton Dickinson) Biosafety level 2 cell culture facility Liver histology lab with Cryostat

microtome 2 Fluorescence microscopes (Zeiss)

Cell/Molecular biology lab includ-ing Elisa plate reader (iMark/Biorad), UV spectrophotometer(GeneQuant), RTqPCR (ABI 7500) and Chemical analyzer (Spotchem EZ)

I-SKINlabandDepartmentofDermatology Histology lab with cryostat and

microtome (Microm HM525 and HM325, respectively)

In vivo image station (4000MM, Kodak) Western blot system (iBlot, Invitrogen) In- and outpatient care, clinical studies

Industrialapplicationfields

In vitro models closely reflecting liver function are urgently needed in: The cosmetic industry, where animal

testing and marketing bans have become final in March 2013, irrespec-tive of the availability of alternative nonanimal tests

The pharmaceutical industry, where in vitro methods become key for early decision making in the drug develop-ment process due to their speed, high

throughput and cost-effectiveness The chemical industry, where safety

testing under REACH regulation is associated with substantial financial costs and high animal consumption

In vitro dendritic and T cell function assays, as well as preclinical animal models, can be used for the identifica-tion of new therapy options for diseases with a strong inflammatory component.

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VrijeUniversiteitBrussel-UZBrussel

Research Center for CardiovascularDiseases www.chvz.be

The CHVZ research center includes different research groups, all interested in the field of cardiovascular diseases. In parallel, a Center for Cardiovascular Diseases is embedded in the patient care of the University Hospital UZ Brussel, providing a unique opportunity to optimize translational research within the field of cardiovascular disease.

Atherosclerosis,valvulopathy,cardiovascularimaging,ionchanneldisorders,geneticcardiacdiseases,atrialfibrillation,clinicalcardiovascularpharmacology,integrationofclinicalpathwaysintheEMD,linkingtheEMDwiththedatamedicalwarehouse

CenterforCardiovascularDiseases(CHVZ)Guy Van Camp - guy.vancamp@uzbrussel.be

HealthInformatics(KWSB)Rudi Van De Velde - rudi.van.de.velde@vub.ac.be

ClinicalPharmacology&ClinicalPharmacy(KFAR)Alain Dupont - alain.dupont@vub.ac.be

Micro CT

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Main study areas

Cardiacimaging-G.VanCampCooperation is organised with the SAL (Small Animal Lab) of the MIMA research group from the Medical Imaging and Physical Sciences research cluster. Elucidate the mechanisms of drug

induced valvulopathy Define the determining factors for the

evolution from aortic valve sclerosis to aortic valve stenosis

Imaging of the vulnerable plaque using nanobodies and fluorescence techniques in an animal model, with the option of implementing it in the clinic

Ionchanneldisorders-P.Brugada The study of heart rhythm disorders,

together with ventricular tachycardia and the risk of sudden death

The study of genetic defects, more spe-cifically the Brugada Syndrome, and the potential link between ion channel dis-orders and neurological disorders

Examine whether morphological and functional abnormalities present in the Brugada Syndrome, can help in the diagnosis and determination of the prognosis of patients with Brugada Syndrome

ClinicalPharmacology-A.Dupont Optimization of the medicine policy in

the hospital through research within the CHVZ. The results of this research can be translated to other departments of the hospital

HealthInformatics-R.VanDeVelde Optimalisation of the integration of IT

in the electronic patient file. One of the first projects will consist of incorporat-ing the clinical heart failure path in the electronic patient file

Equipment& infrastructure

CentrumHart-enVaatziektenUZBrussel(CHVZ) GE and Philips Healthcare ultrasound

systems Software application tools Echopac and

Excellera for post-processing of GE- and Philips Healthcare ultrasound images

Digital biplane and monoplane flat panel coronary angiography systems

All diagnostic interventional tools as fractional flow reserve, intracoronary echocardiography,

All modalities for electrophysiological and ablation techniques including a magnetic navigation system

SmallAnimalLabofMIMAresearchgroup GE Vivid 7 echosystem with dedicated

post-processing software system and probes adapted for small animal imag-ing

SPECT imaging Micro CT Immunofluorescence system Development of nano body imaging sys-

tems

Industrialapplicationfields

Well-developed clinical pharmacologi-cal research Phase III & Phase IV studies with all pharmaceutical companies

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VrijeUniversiteitBrussel-UZBrussel

PublicHealthgf.vub.ac.be/public-health.php

The cluster Public Health joins together 4 research groups, performing basic, translational and medical-sociological research in health economics, health care organization, eHealth and family medicine.

Healtheconomicevaluations,Healthcarepaymentsystems,Financialequityinhealthcare,Healthservicesresearch,Healthpolicy,Innovationsinhealthcare,Evaluationresearch,Socialinequalities,Integratedcare,Chronicdisease,Diabetes,COPD,Heartfailure,E-health,Medicalinformatics,Biostatistics,Data-mining

InteruniversityCenterforHealthEconomicsResearch(I-CHER)Koen Putman - koen.putman@vub.ac.bewww.vub.ac.be/MESO

Organisation,PolicyandInequalitiesinHealth(OPIH)Mark Leys - mark.leys@vub.ac.bewww.vub.ac.be/MESO

FamilyMedicine(HUIS)Jan Vandevoorde jan.vandevoorde@vub.ac.behuis.vub.ac.be

Biostatistics &MedicalInformatics(BISI)Ronald Buyl - rbuyl@vub.ac.bebisi.vub.ac.be

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Main study areas

InteruniversityCenterforHealthEconomicsResearch(I-CHER) Cost-effectiveness studies in health care Examples are : cost-effectiveness stud-

ies on pharmacist-led information technology intervention for medication errors in primary care, health promotion interventions in kindergarten, enhanced women-centred care in prenatal care, health promotion in mental health care

Cost-of-illness studies Examples are: cost-of-illness studies of

acute stroke care, direct medical costs of traffic injuries

Health impact studies of traffic policies (analytic modelling in the evaluation of traffic policies)

Organisation,policyandsocialinequalitiesinhealthcare(OPIH) Evaluation of policy reforms in health care Evaluation of reforms in mental health

care in Belgium Assessing the needs for health servic-

es Developing a method to assess the needs for mental health services in the Brussels area

Health care innovations- Effectiveness, efficiency and accept-

ability of innovations in health care organisation models, including the implementation of technologies

- Inter-organistional networks and collaboration models in a changing health care landscape

- The use of internet by patients and citizens

- Developments in participation models in health care

Socio-economic en sociocultural dis-parities in health services use

FamilyMedicine(HUIS) Integrated health care delivery Integrated care has been defined by the

World Health Organization (WHO) as: The management and delivery of health

services such as that people receive a continuum of health promotion, dis-ease prevention, diagnosis, treatment, disease management, rehabilitation and palliative care services, through the dif-

ferent levels and sites of care within the health system, and according to their bio-psycho and social needs throughout the life course (WHO, 2012).

Research priorities:- Integrated care programmes and mul-

tifaceted intervention strategies for patients with (multiple) chronic care conditions

- Transmural care (from hospital to home care, and vice versa) for patients with multi-morbidity.

- Quality indicators for integrated healthcare delivery

- Development of a conceptual frame-work on multi-morbidity including a complexity analysis at the level of the patient, caregiver and health system.

Other research topics:- Health services accessibility for socio-

economically disadvantaged groups- Sexual behaviour and dysfunctions in

gay men

E-health,MedicalInformatics(BISI): Introduction of Information and

Communication Technology (ICT) in the health system

Electronic Messaging of Health Data Medical prescriptions and medical

record systems ICT for (continuous) medical education ICT for development (ICT4D): ICT in edu-

cation and in the medical sector.

Biostatistics,Data-mining: The development of new algorithms for

statistical data mining and pattern rec-ognition

Adaptive wavelet methods for mining signal data bases, such as Mass Spectra in proteomics and different versions of multivariate decision tree methods for information discovery and modelling of complex medical and pharmaceutical data bases

Design and (multivariate) statistical analysis of clinical trials

Equipment& infrastructure

E-Health,MedicalInformatics: Data center and computer infrastruc-

ture for medical applications Virtual computer-room infrastructure

supporting education and research on the University Medical Center Brussels

Biostatistics,Data-Mining: Apart from the availability of diverse

advanced statistical software tools (SPSS, SAS, R,) the FIDO software plat-form forms a very powerful environ-ment for fast prototyping and devel-opment of pharmaceutical and medical data technology applications tailored to specific users eg. mass spectrometry data analysis in proteomics

Industrialapplicationfields

Expertise in health economic evalua-tions

Supporting health services in imple-menting organisational health care innovation strategies (knowledge bro-kering of evidence)

Data mining and modelling consultan-cies with focus on medical and pharma-ceutical applications.

New multivariate Consensus tree approach was able to discern specific risk patient groups that were not dis-covered using traditional statistical methods.

Latest research in collaboration with WIV, and supported by INNOVIRIS, involves the development of multivari-ate time series models in an epidemio-logical context for monitoring acute respiratory health problems in relation to air pollution in the Brussels region.

Consultancy regarding ICT in the health- and education systems.

Expertise in university development cooperation, project selection and eva-luation

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VrijeUniversiteitBrussel-UZBrussel

MedicalImagingandPhysicalSciences

Different research teams collaborate in an interdisciplinary research effort which encompasses the development and validation of innovative core technologies, their applications in preclinical translational research and the intro-duction of these emerging technologies into clinical diagnostic imaging practice.

Cellularandmolecularimaging,nuclearmedicine,radiology,image-guidedradiotherapy,framelessradiosurgery,radiobiology

MedicalImaging(MIMA)Tony Lahoutte - tony.lahoutte@uzbrussel.be Johan De Mey - johan.demey@uzbrussel.be Thierry Scheerlinck thierry.scheerlinck@uzbrussel.be www.icmibrussels.be

TranslationalRadiationOncologyandPhysics(TROP)Dirk Verellen - dirk.verellen@uzbrussel.be Mark De Ridder - mark.deridder@uzbrussel.be

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Main study areas

MedicalImaging(MIMA) Introducing nanobodies as a generic

method for pre-clinical and clinical molecular imaging

Developing imaging strategies for serial quantitative monitoring of transplanted cell populations

Cardiac imaging for the monitoring of cardiotoxic effects of drugs and for the imaging of the sympathetic innervation of the heart

Development of algorithms for the effi-cient compression of TOF-PET data and for the reconstruction for truncated CT-image data

Pinhole tomography for small-animal imaging

Perfusion imaging Optimization and quality control of

micro-CT systems Radiation dosimetry, quality control and

radiation protection (low dose CT scan-ning)

Spectral CT applications Valorisation of CT contrast agents in

animal models Digital breast tomosynthesis (DBT) Advanced MRI applications (fMRI, DTI,

perfusion) Concordance between high resolution

imaging and human anatomy Hip prosthesis imaging research program Shoulder imaging research program.

TranslationalRadiationOncologyandPhysics(TROP) Radiosensitization of hypoxic tumor

cells by nitric oxide produced intratu-morally by tumor cells, tumor-associat-ed immune cells or hepatocytes

High-precision radiotherapy by follow-ing tumor motion during radiation

Ablative stereotactic radiotherapy for the treatment of colorectal cancer.

Equipment& infrastructure

MedicalImaging(MIMA) Radiochemistry unit for the production

of new radiolabeled molecules for the diagnosis and therapy of various dis-eases and for the routine production of

clinical PET and SPECT radiopharmaceu-ticals.

Nanobody generation unit MicroSPECT: E.Cam 180 Siemens MicroCT: SkyScan 1178 High-Through-

put MicroCT Bioluminescence Imaging: Photo Imager

Biospace Fluorescence Imaging: Fluorescence

Molecular Tomograph FMTTM2500 LX (Perkin Elmer)

Ultrasound Imaging: General Electric Dual energy CT scanner with iterative

reconstruction module: General Electric 750 HD

Prototype Digital Breast Tomosynthesis unit: General Electric

Hard and software for fMRI and DTI experiments (TMS coil, DTI studio, MedINRIA)

Radiation dosimetry lab: TLD reader, humanoid and technical phantoms

TranslationalRadiationOncologyandPhysics(TROP) Vero stereotactic body radiotherapy

(SBRT) system. (joint product of Brainlab and MHI)

Tomotherapy Hi Art system Elekta Sli 15 accelerator Nucletron HDR Ir 192

Industrialapplicationfields

MedicalImaging(MIMA) Clinical imaging services (all modalities,

including fMRI experiments and spectral CT)

Radiation dosimetry services Animal models for imaging Preclinical Imaging Services (optical,

SPECT, CT, Ultrasound, FMT) Clinical PET/CT and SPECT (Phase I, II and

III studies)

TranslationalRadiationOncologyandPhysics(TROP) Cf. Oncology Research Center (ORC)

page 7

18

VrijeUniversiteitBrussel-UZBrussel

DiabetesResearchCenterThe Diabetes Research Center (DRC) develops cell therapeutic strategies for the prevention and treatment of diabetes. It undertakes a translational program for the preservation and replacement of insulin-producing beta cells, which are known to be depleted in type 1 diabetes. A sufficient beta cell mass is needed to improve metabolic control of the patients and to avoid the devastating disease complications. The DRC uses a cell biologic platform to design and moni-tor methods for preclinical testing and clinical trials. The DRCiscomposedof3researchunits spanning cell biological, preclinical and clinical activities, 4 core facilities (functional cytomics, gene expression, confocal microscopy, preclinical models) and a diabetes biobank with human cells, tissue, blood and data. It hosts over 100 scientific, technical and administrative collaborators. The DRC has inte-grated extramural collaborations into an international consortium, the Center for Beta Cell Therapy in Diabetes with an R&D platform, a clinical network, reference centers and bioindustrial partners.

Diabetes,Pancreas,Betacellmass,Acinarcells,Embryonicstemcells,Proliferation,Reprogramming,Transdifferentiation,Regeneration,Animalmodels,Biomarkers,Prediction,Prevention,Betacelltransplantation,Immunotherapy

DiabetesPathologyandTherapy(DIAB) Frans Gorus frans.gorus@uzbrussel.be

CellDifferentiation(DIFF)Luc Bouwens lucbo@vub.ac.be diff.vub.ac.be

BetaCellNeogenesis(BENE)Harry Heimberg harry.heimberg@vub.ac.be bene.vub.ac.be

CenterforBetaCellTherapyinDiabetesDanil Pipeleers daniel.pipeleers@vub.ac.be www.betacelltherapy.org

InsulinGlucagon

19

Main study areas

CellBiologicalbasis

DiabetesPathologyandTherapy(DIAB) Assessment of functional beta cell mass

in situ Identification of (pre)beta cell pheno-

types and their markers Regulation of insulin producing capacity

CellDifferentiation(DIFF) Reprogramming of pancreatic exocrine

acinar cells to endocrine beta cells Directed differentiation of embryonic

stem cells to pancreatic cells

BetaCellNeogenesis(BENE) Generation of a functional beta cell mass

by differentiation, proliferation, matura-tion and survival: identification of the necessary extra- and intracellular factors

In vitro expansion of non-beta cells from mouse and human pancreas and differentiation to functional beta cells

Identification and isolation of beta cell stem/progenitor cells from pancreas of mouse and man

Translationaldevelopment

DiabetesPathologyandTherapy(DIAB) Studies to select biological markers for

detecting and monitoring disease pro-gression and assessing intervention strategies in preclinical models and clin-ical trials: Clinical biology platform for develop-

ment and validation of genetic, hor-monal and autoantibody markers of diabetes

Beta cell proteomics and transcrip-tomics to identify novel biomarkers of beta cell damage

Access to Diabetes Biobank (blood samples, data) for (inter)national studies on the epidemiology and biol-ogy of type 1 diabetes

Stratification of type 1 diabetic patients according to disease state and of relatives according to disease risk: selection and composition of study groups for clinical trials

Detection of beta cell death and mon-itoring of functional beta cell mass during disease and following inter-ventions: surrogate endpoints for clinical trials

Access to Diabetes Biobank (pancreas tissue) to assess functional beta cell mass and inflammation in the pan-creas and their relation to circulating biomarkers (antibodies, genes)

Preclinical models to identify cells and/or compounds to help replace a func-tional beta cell mass through cell trans-plantation or beta cell regeneration: Development of a confined implant

site that can be monitored and modu-lated in order to improve metabolic outcome of a human beta cell graft

Comparison of outcome of primary human beta cell grafts with that of grafts prepared from alternative sources (human embryonic stem cell- derived grafts, reprogrammed human adult differentiated cells, perinatal porcine cells) with the use of various immune-isolation devices

Determination of beta cell numbers in the pancreas of normal and diabetic NOD mice with and without anti-T lymphocyte treatment (anti-CD3)

Effect of compounds on the regen-eration of beta cells in the diabetic pancreas

CellDifferentiation(DIFF) Stimulation of beta cell regeneration in

diabetes with growth factors, cytokines, or phytochemicals

Noninvasive imaging of the pancreatic beta cell mass with biomarkers

BetaCellNeogenesis(BENE) Development of experimental models to

study proliferation and survival of beta cells and (re)programming of non-beta to beta cells

Clinical trials

DiabetesPathologyandTherapy(DIAB) Cell transplantation to restore a func-

tional beta cell mass in type 1 diabetes patients

Arrest of the disease process in early (pre)clinical stages of type 1 diabetes.

More info see www.betacelltherapy.orgwww.bdronline.be

Infrastructureand(major)equipment

DiabetesPathologyandTherapy(DIAB) Functional cytomics core facility

Flow cytometers: FACS Vantage, FACStar Plus (n=2), FACSAria (Becton Dickinson)

Pathway imaging modules (Becton Dickinson Atto Biosciences) for simultaneous detection and sensitive quantification (in space and time) of 8 fluorophores in living cells

Preclinical model core facility Fully equipped labs for animal dis-

section, transplantation, organ- and

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islet isolation, cell culture, histology, immunocytochemistry, fluorescence microscopes, microtomes, molecular biology, clinical biology

Electron microscope and microtome core facility Fully equipped histopathology plat-

form with transmission EM Philips Tecnai 10 and Scanning EM-SEM 505 electron microscopes and 9 microtomes

Diabetes Biobank Sample- and databank from diabet-

ic patients and risk groups with 23 ultralow freezers (-80C) and protect-ed confidential database

Beta Cell Bank in UZ Brussel: GMP facility with 2 fully equipped clean rooms for preparation of clinical grade grafts

Pancreatic tissue bank Clinical biology platform

Fully equipped clinical biology lab in UZ Brussel with automated (immu-noassay) analyzers, liquid scintilla-tion counters, gamma counters, DNA extraction robot

Metabolic unit in UZ Brussel with Phase I clinical trial facility

CellDifferentiation(DIFF) Confocal microscopy core facility

Leica DMIRBE confocal laser scanning microscope TCS-SP1

Fully equipped rooms for histology, fluo-rescence light microscopy, cell & tissue culture, RNA and protein analysis

BetaCellNeogenesis(BENE) Gene expression core facility

Equipment for RNA and DNA ana-lysis: DNA sequencer, Nanodrop, BioAnalyzer, Real time PCR thermal cycler, conventional thermal cyclers, gel electrophoresis

Fully equipped rooms for (i) recombinant adeno- and lentivirus production, (ii) in vivo transduction experiments with adeno- and lentivirus, (iii) islet isolation from mouse pancreas, (iv) isolation and culture of embryonic pancreas, and (v) culturing primary cells and immortalized cell lines

Industrialapplicationfields

DiabetesPathologyandTherapy(DIAB) Diabetes Biobank (included in CMI-

Biobank) comprising >70000 bloodsam-

ples and epidemiological, clinical and biological data from >8000 patients and >9000 relatives aged under 40 years for recruitment of patients for clinical trials and for companies with which DRC collaborates (TolerX, GSK, Peptor, Andromeda)

Development of Drug Screening Platform for testing the potential of compounds to stimulate beta cell growth and differentiation

Preclinical testing of beta cell grafts (with or without alginate encapsulation) derived from perinatal porcine pancre-ata, produced by a DRC spin-off (Beta Cell nv), in preparation of clinical phase I and II trials

Preclinical testing of human embry-onic stem cell-derived grafts (with or without Encaptra-immuno-isolation device) (Via-Cyte)

Celldifferentiation(DIFF) Screening of chemicals for their protec-

tive, mitogenic, and other effects relat-ing to beta cell number in the pancreas

BetaCellDifferentiation(BENE) Definition of a minimal set of signals

that drive the generation and preserva-tion of functional beta cells

VrijeUniversiteitBrussel-UZBrussel

PharmaceuticalResearchandDataTechnologywww.vub.ac.be/farmacie/research/Research.html

The Center for Pharmaceutical Research (CePhaR) consists of four research groups involved in various stages of pharmaceutical R&D, from early lead selection to the assessment of efficacy and safety of finished products. Innovation is the driving force. Our goal is to deal with key bottlenecks in the pharmaceutical R&D process of today, including rational method development, adequate data mining, search for appropriate biomarkers and the develop-ment of better in vivo and in vitro models for human health and disease.

AnalyticalChemistry,Chirality,Chemometrics,Experimentaldesign,Pharmaceuticalanalysis,Neurochemistry,Neuropharmacology,Pharmacokinetics,Microdialysis,Behaviour,Neurovirology,Antiviralcompounds,Poliovirus,TMEV,Multiplesclerosis,Invitrotoxicology,Alternative3Rmethods,Stemcells,Primaryhepatocytes,Cosmeticsafety

AnalyticalChemistryandPharmaceuticalTechnology(FABI)Yvan Vander Heyden yvanvdh@vub.ac.be www.vub.ac.be/fabi/

Associatedgroup1:ExperimentalPharmacology(EFAR)Yvette Michotte ymichot@vub.ac.bewww.vub.ac.be/farmacie/research/fasc.html

Associatedgroup2:PharmaceuticalBiotechnologyandMolecularBiology(MICH)Bart Rombaut- brombaut@vub.ac.bewww.vub.ac.be/MICH/

Associatedgroup3:InVitroToxicologyandDermato-Cosmetology(IVTD)Vera Rogiers- vrogiers@vub.ac.beminf.vub.ac.be/~fafy/

21

22

Main study areas

AnalyticalChemistryandPharmaceuticalTechnology(FABI) Evaluation of the rational use of new

developments in separation techniques. The separation techniques considered are liquid chromatography, capillary electrophoresis and capillary electro-chromatography.

Chiral separations: definition and update of separation strategies by means of different electrophoretic and chromatographic separation techniques.

Fingerprint development for herbal extracts and their data handling

Drug impurity profiling Introduce analytical separation tech-

niques in virology All data analysis of experimental results,

for instance, multivariate calibration aspects on fingerprint data, classifica-tion of different plant species.

ExperimentalPharmacology(EFAR) Studying pathophysiological changes in

the brain in order to define new strat-egies for drug development and drug testing. The group is particularly inter-ested in epilepsy and its comorbidities (e.g. cognitive decline and depression), Parkinsons disease and focal transient brain ischemia.

In vivo microdialysis is used to sample different neurotransmitters and neuro-modulators such as dopamine, seroto-nin, noradrenaline, glutamate, GABA, D-serine and various neuropeptides from specific brain areas in freely mov-ing rodents. The neurochemical data thus obtained are supported by behav-ioural and immunobiological tech-niques.

The group has a strong analytical back-ground and is specialized in the devel-opment of miniaturized LC methods, coupled to fluorescence, electrochemi-cal or tandem mass spectrometric (MS/MS) detection, for the quantification of neurotransmitters and neuromodula-tors in microdialysates. In addition, we have a large experience in the develop-ment and validation of analytical meth-ods for the determination of drugs in

drug products and biological samples with capillary electrophoresis, LC-UV, LC-fluorescence and LC-MS/MS. For some drugs such as anti-epileptics, the microdialysis technique is also applied to study their pharmacokinetics and brain distribution.

PharmaceuticalBiotechnologyandMolecularBiology(MICH) Fundamental research on the replica-

tion cycle of poliovirus, research con-centrates on the first steps of the cycle (adsorption, uncoating) and the last step (assembly);

Development of new poliovaccines (also biotech vaccines);

Fundamental research on antiviral com-pounds (in collaboration with Janssen Research Foundation);

Viruses on the origin of multiple sclerosis?

Theilers murine encephalitis virus (TMEV), a mouse model for multiple sclerosis.

InVitroToxicologyandDermato-Cosmetology(IVTD) In vitro toxicology:

- Development of metabolically-com-petent in vitro liver models based on: a) Primary hepatocytes by (i) explor-

ing epigenetic mechanisms of gene regulation i.e. histone acetylation, DNA methylation, microRNAs (ii) investigation of the role of inter-cellular communication and (iii) immortalization of primary hepat-ocytes,

b) Stem cells isolated from various human postnatal tissues, i.e. skin, adipose tissue and Whartons jelly, by (i) careful characterization, (ii) in vitro expansion and (iii) differen-tiation towards the hepatic pheno-type,

c) A coating substratum and 3D cell cultivation scaffold derived from decelullarized liver matrix.

- Safety assessment of chemato-cos-metic based on non-invasive bioengi-neering and in vitro methodology.

Clinical research: Targeting intercellular communication in

the treatment of acute and chronic liver diseases and potential use of stem cells in disorders of the central nervous system.

Equipment& infrastructure

AnalyticalChemistryandPharmaceuticalTechnology(FABI) Ultrahigh pressure liquid chromatogra-

phy system coupled to mass spectrom-eter

Shimadzu gradient ultrafast liquid chro-matography (UFLC) system with diode array detection

Supercritical fluid chromatography sys-tem with diode array detection Thar Method station II

ELSD detector Alltech ELSD 2000 Merck-Hitachi Lachrom Elite Gradient

HPLC system with diode array detection Capillary electrophoresis Agilent

HP3DCE system with diode array detec-tion

2 x Merck-Hitachi Lachrom gradient HPLC systems with UV detection

2 x Capillary electrophoresis Beckman P/ACE MDQ systems with diode array detection and Laser induced fluores-cence detection

NIR spectrophotometer Bran+Luebbe InfraAlyzer 500

Ecocell 111 liter incubator Pressurized capillary electrochromatog-

raphy system Unimicro-Trisep 2100 GV UV/Vis spectrophotometer Shimadzu

UV-2101PC Nitrogen generator Permea CPA1 Plasma cleaner/sterilizer Harrick Plasma

ExperimentalPharmacology(EFAR) Broad range of rodent models:

- Chemical and electrical models for epileptic seizures and chronic epilepsy

- 6-hydroxydopamine model for Parkinsons disease: striatal, MFB and nigral lesioning

- Endothelin-1 model for focal tran-sient cerebral ischemia

Rodent behavioural unit:- Locomotor activity: open field, rota-

tional behaviour (Rotometer), neuro-logical deficit score, Rotarod

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- Spatial memory: Morris water maze for rats and mice; Y maze for mice

- Anti-depressant-like activity: forced swim test, tail suspension test

Stereotaxic surgery (rat and mouse) and in vivo microdialysis

Telemetry-based 24h video-EEG moni-toring units for rodents

PK/PD modelling Broad range of analytical equipment:

- Liquid chromatography with electro-chemical, fluorescence or ultraviolet detection for the quantification of neurotransmitters and drugs

- Nano liquid chromatography coupled to tandem mass spectrometry for the deter-mination of neuropeptides and drugs

- Capillary electrophoresis- Size exclusion chromatography

Doppler flowmetry Immunobiotechnological techniques:

(immuno)histochemistry, Western blot-ting, ELISA

PharmaceuticalBiotechnologyandMolecularBiology(MICH) Biologic duoflow (Fast Protein

Liquid Chromatography) with IMAC-purification, size exclusion and hydro-phobic interchange column)

Biosafety level 2(+) laboratories Cell culture facilities Virus culture facilities Liquid handling system (robot) Perkin

Elmer Multiprobe II with gripper Liquid handling system (robot) Perkin

Elmer Multiprobe II with shaking Spectrofotometer Nanodrop ND 1000

UV-Vis Liquid scintillation counter Wallac1409 Biotek Microplate Fluorescence Reader

FL600 Asys Microplate Reader Expert 96 Luminescent Image Analyzer

ImageQuant LAS4000 Capillary electrophoresis system

Beckham Coulter P/ACE MDQ system with Diode array detector (FABI)

Shaking incubator (Barnstead MaxQ 5000) - max 6 x 2l

Ultracentrifugation (swingout and fixed angle)

PCR Perkin Elmer GeneAmp PCR system 2400

Immunobiotechnological techniques: Western blotting, ELISA, affinity capture assay

Standard virological techniques: plaque titration, infectivity assays

InVitroToxicologyandDermato-Cosmetology(IVTD) Biosafety level 2 laboratory and culture

facilities Organ perfusion unit Scintillation counter (TriCarb 2810 TR;

Perkin Elmer) Fluorescence microscope (Nikon

Eclipse Ti) 2 RTqPCR termal cyclers (Step One Plus;

Applied Biosystems, iQ5; Bio-Rad) Microplate reader (Victor3; Perkin-

Elmer) Micro-volume UV spectrophotometer

(NanoDrop 2000c; Thermo SCIENTIFIC)

Industrialapplicationfields

AnalyticalChemistryandPharmaceuticalTechnology(FABI) Chiral screening approaches/protocols Data analysis (classification, modelling)

of any kind of experimental results Quality control of herbal extracts Fast separations Impurity profiling/orthogonal systems

ExperimentalPharmacology(EFAR) Predictive neuropharmacology:

- Screening of new chemical entities in different animal models for neuro-logical diseases

- Evaluation of clinically used drugs- Unravelling pathophysiological pro-

cesses- Unravelling new potential mecha-

nisms of action, drug targets- Prediction and modulation of blood-

brain-barrier passage and active efflux systems

Biomarkers:- Determination of disease-related bio-

markers: neurotransmitters, neuro-peptides, etc

- Mechanism-based pharmacokinetic and pharmacodynamic modelling using neurotransmitters as biomark-

ers for predicting drug effects in the brain and drug efficacy based on drug plasma concentrations

PharmaceuticalBiotechnologyandMolecularBiology(MICH) Development of new poliovaccines (also

biotech vaccines) Fundamental research on antiviral com-

pounds Fundamental research on and develop-

ment of nanobodies

InVitroToxicologyandDermato-Cosmetology(IVTD)Assessment of hepatotoxic potential of new chemical entities is an essential and hence legally required step in the devel-opment of safe cosmetic, pharmaceutical and chemical products. Therefore, in vitro models closely reflecting liver function are urgently needed in: The cosmetic industry, where ani-

mal testing and marketing bans have become final in March 2013, irrespective of the availability of alternative non-animal tests,

The pharmaceutical industry, where in vitro methods become key for early decision making in the drug develop-ment process due to their speed, high throughput and cost-effectiveness,

The chemical industry, where safety testing under REACH regulation is asso-ciated with substantial financial costs and high animal consumption.

24

VrijeUniversiteitBrussel-UZBrussel

Reproduction,GeneticsandRegenerativeMedicine rgrg.vub.ac.be

The research cluster Reproduction, Genetics and Regenerative medicine consists of 7 research groups and is linked to the Center for Medical Genetics, the Center for Reproductive Medicine and the Department of Pediatrics of the UZ Brussel, allowing to perform basic, translational and clinical research.

Human preimplantation embryo, Human embryonic stem cell, Neuro-paediatrics, Children follow-up,Cardiogenetics,Spermatogonialstemcell,Spermatogenesis,Maleinfertility,Fertilitypreservation,Implantation,Endometrium,Embryo,Immunology,Pretermbirth,Fetalfibronectin,Bacterialvaginosis,Cytomegalovirus,prenataldiagnosisandpredictionofsequellae,HereditaryNeurologicalDisorders,MitochondrialCytopathies,MalformationsofCorticalDevelopment,Genetherapy,iPS,Hereditarydisease,Genetics,Regenerativemedicine

ReproductionandGenetics(REGE)Karen Sermon - ksermon@vub.ac.be

BiologyoftheTestis(BITE)Herman Tournaye - htournay@uzbrussel.be

FollicularBiology(FOBI)Johan Smitz - jsmitz@uzbrussel.be

ReproductiveImmunologyandImplantation(REIM)Claire Bourgain - cbourgai@vub.ac.be

MotherandChild(MOKI)Gilles Faron - gilles.faron@uzbrussel.be

Neurogenetics(NEGE)Linda De Meirleir - ldmeirle@uzbrussel.be

GeneTherapyandRegenerativeMedicine(GTRM)Thierry VandenDriessche - thierry.vandendriessche@vub.ac.beMarinee Chuah - marinee.chuah@vub.ac.be

25

Main study areas

ReproductionandGenetics(REGE) Mitochondrial diseases and malforma-

tions of the cortical development and their causes

Genetic aspects of male infertility Preimplantation genetic diagnosis (PGD)

both for monogenic diseases and chro-mosomal aberrations

Assessing the safety of ART techniques: research project on the epigenetics of human development

Mechanisms that underlie totipotency in human preimplantation embryos

Long-term follow-up of children born after Assisted Reproductive Technology

Research on human embryonic stem cells and induced pluripotent stem cells

Research project on cardiogenetics focused on Brugada syndrome in close collaboration with the Research Center for Cardiovascular Diseases of the UMC

BiologyoftheTestis(BITE) Feasibility of storing spermatogonial

stem cells (SSCs) either as a suspension or as whole tissue

Transplantation of SSCs by infusion of a cell suspension or by tissue grafting

Strategies for optimizing the regenera-tion of spermatogenesis from SSCs

Feasibility and safety of reproduction with gametes obtained after transplant-ing SSCs

Strategies for preventing the loss of germ cells by gonadotoxic treatments

Strategies for preventing the loss of germ cells in genetic diseases, eg Klinefelters syndrome.

Generation of sperm cells in-vitro Use of SSCs in regenerative medicine

FollicularBiology(FOBI) Storage of ovarian tissue via freezing Research into molecular indicators of

egg cell quality Research into safety of in vitro methods

to mature gametes Research on In Vitro Maturation (IVM)

of human oocytes retrieved from small follicles

Research Bioassays

ReproductiveImmunologyandImplantation(REIM)The research group studies the different aspects of early implantation, especially endometrial - embryo interaction and pro-cesses involved in succesfull natural and IVF cycles. Endometrial study areas

- Endometrial morphology in natural and IVF cycles in relation to receptivity

- Molecular pathways in endometrial receptivity with microarray and sub-sequent RT-PCR Key role of the COX-2 pathway in

the endometrium of IVF cycles with subsequent ongoing pregnancy

Specific endometrial gene clus-ters involved in different IVF stimu-lation protocols in oocyte donors

- Endometrial immune system in repeated implantation failure Distribution and function of uter-

ine dendritic cells and their derived cytokines from endometrial tissue and fluid aspirates to an in-vitro model

Endometrial natural killer cells and their killer cell immunoglobulin like receptors in endometrial from patients with recurrent implanta-tion failure, miscarriage and pre-eclampsia

Embryo study areas- Expression of HLA in embryos and

follicle fluid, more specifically HLA-C, G and E and combinations of HLA and their KIR receptors Expression of HLA-G in embryos

and embryonic stem cells Soluble HLA and cytokines in

embryonic culture supernatant and follicle fluid

HLA-G function in human embry-onic stem cells

HLA genotyping of embryos in recurrent miscarriage

- Cross-talk between the embryo and the endometrium Development of a standard

implantation model for embryo attachment and early invasion in an Ishikawa cell line

Investigation of implantation regulators in the human embryo

MotherandChild(MOKI) Screening of preterm birth - Fetal fibronectin test as a screen-

ing tool in a low-risk population: does recent coitus interfere with its interpre-tation. Comparative prospective study.

- Ureaplasma: does the sampling loca-tion matter? Prospective study.

- Does the PCR test predict better pre-term birth than the Ureaplasma culture? Prospective study.

- Is there a link between these different screening tools? Comparative prospec-tive study.

Urinary infection during pregnancy: When is it more appropriate to screen for asymptomatic bacteriuria: during the first or during the second trimester? A prospective comparative study.

Cytomegalvirus(CMV) and pregnancy - Prenatal diagnosis of CMV:

Prediction of sequellae in con-genital infected children (viral load in amniotic fluid,contribution of ultrasound,fetal MRI)

In twin pregnancies - Elaboration of a screening model for

CMV infections during pregnancy

Neurogenetics(NEGE) The development of diagnostic, bio-

chemical and molecular methods; the prevention; and the study of treatment of mitochondrial cytopathies

The identification of genes involved in the regulation of neuronal migration and the study of the functional con-sequences of mutations in these genes by combining patient-driven molecular genetic studies and comparative genetic research in zebrafish models

GeneTherapyandRegenerativeMedicine(GTRM)Convincing evidence continues to emerge from clinical trials that gene therapy is yielding therapeutic effects in patients suffering from a wide range of diseases. The Department of Gene Therapy and Regenerative Medicine (GTRM) continues to build on our 20 years experience in this field and focuses primarily on the develop-ment and validation of gene and (stem) cell therapy for major health- and life-

26

threatening genetic disorders, including hemophilia and neuromuscular disorders (Duchenne and myotonic dystrophy). We are actively conducting translational gene therapy studies in small and large animal models, in anticipation of moving forward towards clinical trials. To achieve this goal we have consolidated a broad state-of-the-art technology platform based on the latest viral vectors (retroviral, lenti-viral, AAV), non-viral vectors (PB and SB transposons), genome engineering systems (designer nucleases -TALEN) and stem cell technologies (progenitor stem cells and iPS).

Equipment& infrastructure

ReproductionandGenetics(REGE) State-of-the-art IVF center (CRG) with

more than 5000 cycles per year, provid-ing scarce patient material for research. This includes sperm, oocytes, embryos surplus to IVF treatment and donated by the patients, and embryos created for research.

Fully equipped medical genetics center, with infrastructure such as a cytoge-netics lab, microarray and sequencing facilities, standard molecular biology infrastructure, and a large collection of archived patient material. This includes extracted DNA, skin fibroblast cul-tures, prenatal tissue cultures and EBV-transformed lymphoblast cell lines.

Research lab closely integrated with the two previous labs, with separate culture rooms for human and animal work, con-focal and fluorescent microscopy and molecular biology facilities. More than 28 hESC lines are available for other researchers through an MTA

BiologyoftheTestis(BITE)The BITE laboratory is part of the medi-cal genetics department. We have two cell culture rooms (one for mouse and one for human cells) with one horizontal flow and incubator in each room. We share the pre-and post-PCR room, the staining room (with vertical flow), the imaging room (with two confocal and one fluorescence microscope) and the cold room with the REGE and the FOBI lab. There is also space available for a -20C freezer, the mQ water

dispenser and two sterilization ovens. Access to FACS, ultrasound-guided injec-tions and imaging and tissue sectioning and paraffin embedding.

FollicularBiology(FOBI) Diagnostics: molecular biology tests:

oocyte quality testing Cell culture media companies: oocyte

maturation media Pharmaceutical companies: reprotoxic-

ity testing

MotherandChild(MOKI) RapidFFN test Analyser kit

Neurogenetics(NEGE) Histology and immunohistochemistry

facility qRT-PCR facility Microarray Next Generation Sequencing Biochemical analysis in collaboration with

UZ Gent (Prof. R. Van Coster) Zebrafish morpholino knockdown mod-

els in collaboration with KUL (Prof. P. De Witte)

Gene Therapy and RegenerativeMedicine(GTRM)Fully equipped P2 laboratory suites and molecular biology laboratories equipped with laminar flows, ultra-centrifuges, incubators, quantitative PCR, fluorescence microscopes. Access to FACS and confocal core facilities, etc.

Industrialapplicationfields

ReproductionandGenetics(REGE) Pharma in the field of fertility drugs:

CRG conducts large studies with several partners

Products for the IVF lab: CRG IVF lab conducts large studies with several part-ners

BiologyoftheTestis(BITE)The UZ Brussel already started the bank-ing of testicular tissue from prepubertal patients. The testicular tissue banking has a non-profit character. Since this testicular tissue bank is unique in Flanders, the UZ

Brussel could act as a reference lab with the intention that also other institutes can benefit from our knowledge. Being a ref-erence lab will not only attract Belgian patients, but also patients from other countries, stressing the role of Flanders and Belgium as a medical reference region. The system for in-vitro spermatogenesis could be developed further into a patenta-ble screening assay for studying the phar-macotoxicological properties of existing or new chemical molecules. Such a system could possibly reduce or replace animal testing. Furthermore, in-vitro spermato-genesis may enhance our knowledge about regulatory mechanisms during spermato-genesis, giving a boost to the development of male contraceptives.

ReproductiveImmunologyandImplantation(REIM) Development of a standard test for

endometrial receptivity Development of a standard test for

embryonic implantation capacity

Gene Therapy and RegenerativeMedicine(GTRM) Development and validation of

Advanced Therapy Medicinal Products (ATMPs)

Gene therapy Functional genomics Regenerative medicine Induced pluripotent stem cells (iPS) Genome engineering (TALEN, transposons)

27

VrijeUniversiteitBrussel-UZBrussel

Development,AgeingandPathology gf.vub.ac.be/development-ageing-and-pathology.php

The research of the cluster Development, Ageing & Pathology focuses on 3 major research niches: Developmental aspects Environmental aspects Degenerative & age-related aspects

The prioritary research lines of this cluster are mainly linked to the specificity of its 7 research groups.

InternalMedicineSpecializations(INTG)Brigitte Velkeniers - brigitte.velkeniers@uzbrussel.beEndocrinology: Kris Poppe - kris.poppe@uzbrussel.be Nephrology: Christian Tielemans - Christian.tielemans@uzbrussel.be Pneumology: Sylvia Verbanck - sylvia.verbanck@uzbrussel.be Research Methodology and Rheumatology: Patrick Haentjens - patrick.haentjens@uzbrussel.be Intensive Medicine: Herbert Spapen - Herbert.spapen@uzbrussel.be

FrailtyinAgeing(FRIA)Ivan Bautmans - ivan.bautmans@vub.ac.beIngo Beyer - ingo.beyer@uzbrussel.bewww.vub.ac.be/FRIA

ResearchGrouponEmergencyandDisasterMedicine(ReGEDiM-URGE)Ives Hubloue - ives.hubloue@uzbrussel.beMichel Debacker - michel.debacker@vub.ac.beregedim.vub.ac.be

Pediatrics(GRON)Yvan Vandenplas - yvan.vandenplas@uzbrussel.be Jutte Van der Werff ten Bosch - jutte.vanderwerfftenbosch@uzbrussel.be

Microbiology(MIPI)Denis Pierard - denis.pierard@uzbrussel.be Frans Gordts - frans.gordts@uzbrussel.be

Surgery(HEEL)Georges Delvaux - georges.delvaux@uzbrussel.be

Anesthesiology(ANES)Jan Poelaert - jan.poelaert@uzbrussel.be

28

Main study areas

InternalMedicineSpecializations(INTG) Endocrinology: Thyroid disorders and

infertility Nephrology: Hemodialysis, kidneylithia-

sis and medication injuries of the podo-cytes and protenuria

Pneumology: Lungmodels and ventila-tiondistribution, lungsaving radiation after breast amputation and nanoparti-cles in the context of aerosoltherapy

Research methodology and rheuma-tology: Meta-analyses of hipfractures and European Male-Ageing study

Intensive medicine: renal failure and renal function replacement therapy, indirect calorimetry for optimalisation of the nutrition policy in intensive care (IC) and new ventilation techniques in IC

The Frailty in Ageing Research (FRIA) department conducts a comprehensive research program to untangle the underly-ing mechanisms and to develop interven-tions for prevention and rehabilitation of frailty in the ageing. Effect of physical training on immu-

nosenescence (inflammation, senescent cells), sarcopenia (age-related muscle atrophy), dynapenia (age-related muscle weakness) and cognition: Senior PRoject INtensive Training (SPRINT)

Effect of inflammation on sarcope-nia and muscle weakness: interven-tion with anti-inflammatory products, role of infections in the elderly, role of Advanced Glycation End products (AGE).

Identification and characterization of senescent cells: T-lymphocytes, influ-ence of chemotherapy, influence of cor-ticoids

Motivational aspects of physical exer-cise and active ageing

Early detection of dementia and mild cognitive impairment

The Research Group on Emergency andDisaster Medicine (ReGEDiM-URGE) conducts a research program focused on different aspects of both emergency and disaster medicine : Emergency Medicine: training, qual-

ity assessment and quality improve-

ment, Information Technology (IT)-applications, data-management and process-analysis, outcome predictors in emergency medicine, cardiopulmonary resuscitation, developments in medical imaging techniques, patient satisfac-tion and patient information, geriatric & pediatric emergency care (EC).

DisasterMedicine: evidence-based dis-aster medicine, modelling and simula-tion of disasters and disaster medical management, disaster medical manage-ment, disaster mental health, disaster ethics.

Pediatrics(GRON) Pediatric pneumology: epidemiol-

ogy/microbiology in otherwise healthy children (community acquired pneu-monia (CAP) and persistent wheezing, CAP complicated with empyema) and in cystic fibrosis patients (CF) (Biofilm formation, S. aureus, Burkholderia cepa-cia, respiratory viruses), immunological response (Pertussis and Tuberculosis), new diagnostics in CF (Nasal potential differentials), new treatments in CF, and pharmacological studies (asthma medi-cation, CF new treatments, evaluation of vaccines), and participation in several multicentric studies (infectiology, CF)

Pediatric gastroenterology: milk allergy, gastro-oesophageal reflux and Crohns disease

Pediatric hematology-oncology andimmunology: cooperation in interna-tional intervention studies in childhood cancers, studies concerning supportive care aspects in childhood cancer, stud-ies in a coagulation disorders/immuno-globulin substitution therapy phase II trial, cooperation with several interna-tional partners for patient based reseach in primary immunodeficiencies, defects in the innate immune system, manage-ment of invasive fungal infections

Deontology & Ethics: deontological, ethical and legal implications of the care for minors

Pediatric Nephrology: study for Aliskiren in pediatric patients with hypertension

Neonatology: cooperation in multi-center interventional randomized con-

trolled studies (e.g. SToP-BPD trial), cooperation with international studies on pharmacokinetics and pharmacody-namics of drugs in newborn infants (e.g. Pharmacool study), involvement in the international Cochrane Collaboration (meta-analysis, individual patient data meta-analysis)

MIPI - Microbiology and InfectionPrevention: Microbiology: Diagnosis, treatment

and epidemiology of infectious diseases, especially pertussis, diphtheria, legionel-losis, Verotoxin-producing E. coli infec-tions, new bacterial identification tech-niques, Burkholderia cepacia complex in cystic fibrosis patients, anaerobic infec-tions & antibiotic sensitivity, HIV infec-tion and AIDS, and congenital infections (cytomegalovirus (CMV), toxoplasmosis)

Infection Prevention: surveillance and prevention of nosocomial infections

Ear, nose and throat: Hearing loss and congenital CMV infection, sinusi-tis, assessment of the influence of nasal versus oral breathing on the craniofacial development.

ThedepartmentofSurgery(HEEL) works in close collaboration with the Diabetes Center of the UZ Brussel: Neural influence in the resolution of

type 2 diabetes mellitus after Roux-en-Y gastric bypass in patients with morbid obesity

Clinical application of beta cells trans-plantation in type 1 diabetes

Nutrition and cancer Research into the neurogenic influence

through the nervus vagus on oxidative stress at the periphery (o.a. adipose tis-sue) and chronic inflammation in the metabolic syndrome

Lymphedema & breastcancer Gastrointestinal Tumors (GIST): Analysis

gene-mutation/ Open versus laparo-scopic intervention

The department of Anesthesiology andPerioperativeMedicine(ANES) conducts both experimental and clinical studies with respect to pathophysiology of pain, other inflammatory pathways (induced by

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ischaemia, infarction, surgery, hypother-mia) and pharmacokinetic and dynamic studies of anesthetics. TRPV receptors on the aortamodel and

in an in vivo model (animal research) Xenon anesthesia (in the context of

inflammation experimental research and later clinical)

Online lung aeration in ventilated patients (various protocols running con-secutively)

Thoracoscopic ablation and postopera-tive pain

Adjuvantia in local anesthestics Acute renal insufficiency (AKI) in post-

operative patients Thoracic epidural analgesia and cardiac

function in 1- and 2-lung ventilation Pharmacokinetics and pharmacodynam-

ics of anesthetics

collaborationsbetweenresearchgroupsinspecificprojects Interaction of thyroid disorders with

reproduction and pregnancy: INTG and GRON

Infection in cystic fibrosis patients: INTG, GRON and MIPI

Muscle weakness as a parameter at the arrival in EC: INTG, URGE and FRIA

Lung models and ventilation distribu-tion: age-related changes and pathol-ogy: INTG, GRON and FRIA

Influence of medical and surgical treat-ment of pituitary disorders: INTG, HEEL and FRIA

Pulmonary function in elderly partici-pants of the Senior Project Intensive Training (SPRINT): FRIA and INTG

Renal function in high risk surgery: INTG and ANES

Influence of anti-inflammatory prod-ucts on perioperative intervention: HEEL and FRIA

Outcome of geriatric patients who needed endotracheal intubation in the pre-hospital and in-hospital setting: FRIA and URGE

Connection between drug use and the functional status of the geriatric patient at the EC: URGE and FRIA

Respiratory infections in children: MIPI and GRON

Medication history reconciliation by

clinical pharmacists in patients admitted to the emergency department. (+ FARC): URGE and MIPI

A philosophical and ethnographic study of medical diagnostics. Literature meets practice (INTG and URGE)

Assessing and improvement of drawing procedure of blood cultures in the emer-gency department. (MIPI and URGE)

Drug use review: empiric antibiotic therapy in the emergency department. (+FARC) : MIPI and Urge

Pediatric aspects in emergency medi-cine: URGE and GRON

Treatment of acute pain in the ER: URGE and ANES

Equipment& infrastructure

FRIA: Laboratory facilities and knowhow for Determination of markers of inflamma-

tion: circulating (cytokines, chemokines, heat shock proteins, ), intracellular (heat shock proteins, senescence mark-ers), surface markers in peripheral blood mononuclear cells

Cell cultures Muscle biopsies Surface EMG Muscle performance Physical performance, reaction-time

and cognitive testing

ReGEDiM-URGE: simulation and video-conference room for conducting model-ling and simulation exercises and applied research in disaster medical management (hardware and software)

GRON: expertise and a fully equipped lungfunction laboratory for measurements of lungfunction in children, expertise and material for flexible and rigid bronchos-copy in children

MIPI: a full equipped laboratory for the different aspects of microbiology is avail-able, including cell cultures for virol-ogy, molecular biology, L3 security lab for tuberculosis, MALDI-TOF mass spectrom-etry for identification of bacteria. For Ear, Nose and Throat research purposes, exten-

sive audiometrical equipment is present. Also, access to Cone-beam CT is available and close collaboration with the col-leagues of the department of Orthodontics (SOPA) and their equipment is possible

HEEL:metabolic unit, indirect calorimetric measurements and most recent laproscop-ic techniques

ANES:PulmoVista 500 to evaluate venti-lation adequacy at the bedside, availabil-ity of an anesthesia machine equipped to deliver Xenon

Industrialapplicationfields

FRIA:Physical training programs specially designed for elderly persons

ReGEDiM-URGE: the research on simu-lation and modelling performed by the reseachgroup resulted in the industrial development of different software pro-grams (ISEE, XVR, Victim Base) who are distributed worldwide to emergency res-cue services dealing with the acute medi-cal response in mass casualty and disaster settings

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Publishersimprint

ContributorsOncology Research Center - C4N, Center for Neurosciences - Liver and Cell Biology and Toxicology - Research Center for Cardiovascular Diseases - Public Health - Medical Imaging and Physical Sciences - Diabetes Research Center - Pharmaceutical Research and Data Technology - Reproduction, Genetics and Regenerative Medecine - Development, Ageing and Pathology.

FinaleditingAude Bonehill, Alena Aga

PhotographsGreet De Gendt, UZ Brussel Communication department, research clusters in this brochure (see contributors)

CoverphotographsUZ Brussel Communication department/operating room - Greet De Gendt/Pharmaceutical Research and Data Technology - Oncology Research Center - Liver and Cell Biology and Toxicology - Reproduction, Genetics and Regenerative Medecine - C4N, Center for Neurosciences

Design&LayoutKarel Van den Keybus - Gekko - info.gekko@telenet.be

ResponsiblePublisherSonja HaesenTechnology Transfer InterfaceVrije Universiteit BrusselPleinlaan 2 | B-1050 Brussels | Belgium

The matters covered by this prospectus are subject to change. The university is not responsible for the content of any website addresses in this publication which do not form part of the Vrije Universiteit Brussel domain (vub.ac.be).

University Medical Center

University Medical Center Research Manager: Aude Bonehill, PhD+32 (0)2 477 55 50 | abonehill@uzbrussel.be | www.uzbrussel.be

UMCOM | Laarbeeklaan 101 | B-1090 Brussels | Belgium

VrijeUniversiteitBrusselTechnologyTransferInterface

- We take care of the VUBs knowledge transfer and business development -

Coordinator Technology Transfer Interface: Sonja Haesen, PhD+32 (0)2 629 22 07 | rd.interface@vub.ac.be | www.vubtechtransfer.be

VUB-TTI | Pleinlaan 2 | B-1050 Brussels | Belgium

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